1. Technical Field
This document relates to methods and materials involved in reducing cardiac xenograft rejection. For example, this document provides methods and materials for preparing transgenic pigs expressing reduced or no endogenous Sda, reduced or no endogenous SDa-like glycans derived from the porcine β1,4 N-acetyl-galactosaminyl transferase 2 (B4GALNT2) glycosyltransferase, and/or reduced or no endogenous α-Gal antigens, methods and materials for modifying a xenograft recipient's immunological response to non-Gal antigens (e.g. CD46, CD59, CD9, porcine endothelial cell protein C receptor (PROCR) and annexin A2 (ANXA2)) to reduce cardiac xenograft rejection, and methods and materials for monitoring the progression, if any, of xenotransplant immunologic rejection.
2. Background Information
There is a chronic shortage of organs for transplantation. This is particularly the case in cardiac transplantation where approximately 2300 heart transplants are performed annually but up to 50,000 patients in chronic heart failure could benefit from a transplant. Xenotransplantation (transplantation from one species to another) could provide an unlimited supply of organs if successful. Xenotransplantation can be limited by an immunological rejection of the transplanted organ. Initially this rejection can be due to preformed antibodies present in humans and Old World primates that bind to a carbohydrate modification called the α-Gal antigen. This antigen can be produced in great abundance in pigs and other mammalian species. The combination of abundant α-Gal antigen in pig organs and high levels of preformed anti-Gal antibody in nonhuman primates (a model for humans) can result in a devastating hyperacute rejection of the graft usually within hours.